Expression of epithelial-mesenchymal transition-associated proteins and proliferating cell nuclear antigen in dihydropyridine-induced gingival overgrowth fibroblasts: A preliminary study

Po-Han Chen; Yaw-Tung Chuang; Chiung-Fang Huang; Hsein-Kun Lu

doi:10.1016/j.jds.2022.08.025

Expression of epithelial-mesenchymal transition-associated proteins and proliferating cell nuclear antigen in dihydropyridine-induced gingival overgrowth fibroblasts: A preliminary study

J Dent Sci. 2023 Apr;18(2):551-559. doi: 10.1016/j.jds.2022.08.025. Epub 2022 Sep 17.

Authors

Po-Han Chen¹, Yaw-Tung Chuang², Chiung-Fang Huang^{1

3}, Hsein-Kun Lu^{1

2}

Affiliations

¹ Division of Periodontics, Department of Dentistry, Taipei Medical University Hospital, Taipei, Taiwan.
² School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan.
³ School of Dental Technology, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan.

Abstract

Background/purpose: The clinical features of dihydropyridine-induced gingival overgrowth (DIGO), including extracellular matrix accumulation and cell hyperplasia, are regulated by inflammatory factors (e.g., Interleukin-1β [IL-1β]) in combination with calcium channel blockers (e.g., nifedipine [Nif]). We speculated that IL-1β and Nif (IL-1β/Nif) may be the main factor modulating the proliferative potential and turnover of fibroblasts in DIGO.

Materials and methods: We cultured four DIGO fibroblast strains and analysed the possible effects of IL-1β/Nif treatments on epithelial-mesenchymal transition (EMT)-associated proteins. We developed short hairpin ribonucleic acids (shRNAs) and used them to explore the role of IL-1β/Nif in regulating proliferating cell nuclear antigen (PCNA) levels in DIGO tissues.

Results: Our results revealed that compared with control cells, DIGO cells stimulated with IL-1β/Nif had higher levels of the EMT-associated proteins Snail, Slug, and Twist. Moreover, both drugs enhanced androgen receptor (AR), Slug, and PCNA expression.

Conclusion: Taken together, our data indicate that proinflammatory cytokines in combination with calcium channel blockers can regulate the expression of EMT-associated proteins and increase the proliferative potential of DIGO fibroblasts.

Keywords: Dihydropyridine-induced gingival overgrowth; EMT-associated proteins; Interleukin-1β; Nifedipine; PCNA.